Long-term propranolol use in severely burned pediatric patients: a randomized controlled study

Abstract

Objective: To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns.

Background: Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response. Whether propranolol administration for 1 year after injury provides a continued benefit is currently unclear.

Methods: One-hundred seventy-nine pediatric patients with more than 30% total body surface area burns were randomized to control (n = 89) or 4 mg/kg/d propranolol (n = 90) for 12 months postburn. Changes in resting energy expenditure, cardiac function, and body composition were measured acutely at 3, 6, 9, and 12 months postburn. Statistical analyses included techniques that adjusted for non-normality, repeated-measures, and regression analyses. P < 0.05 was considered significant.

Results: Long-term propranolol treatment significantly reduced the percentage of the predicted heart rate and percentage of the predicted resting energy expenditure, decreased accumulation of central mass and central fat, prevented bone loss, and improved lean body mass accretion. There were very few adverse effects from the dose of propranolol used.

Conclusions: Propranolol treatment for 12 months after thermal injury, ameliorates the hyperdynamic, hypermetabolic, hypercatabolic, and osteopenic responses in pediatric patients. This study is registered at clinicaltrials.gov: NCT00675714.

Figures

FIGURE 1

Patient enrollment diagram.

FIGURE 2

Effect of propranolol on cardiac and metabolic indices. (a) Percent predicted heart rate. (b) Rate pressure product. (c)Resting energy expenditure (REE), expressed as the percentage of energy expenditure predicted by the Harris Benedict equation. In a-c, data are shown as the Loess-smoothed trend with shading indicating SEM.

FIGURE 2

Effect of propranolol on cardiac and metabolic indices. (a) Percent predicted heart rate. (b) Rate pressure product. (c)Resting energy expenditure (REE), expressed as the percentage of energy expenditure predicted by the Harris Benedict equation. In a-c, data are shown as the Loess-smoothed trend with shading indicating SEM.

FIGURE 2

Effect of propranolol on cardiac and metabolic indices. (a) Percent predicted heart rate. (b) Rate pressure product. (c)Resting energy expenditure (REE), expressed as the percentage of energy expenditure predicted by the Harris Benedict equation. In a-c, data are shown as the Loess-smoothed trend with shading indicating SEM.

FIGURE 3

Effect of propranolol on body composition. (a) Percent change in central mass, (b) percent change in truncal fat, and (c) percent change in peripheral lean mass. In a-c, data are expressed as percent change from patient baseline and are shown as the Loess-smoothed trend with shading indicating SEM. (d, e) Comparison of the likelihood of losing ≥5% of (d) total bone mineral content/total body mass (TBMC/TBM) and (e) total lumbar bone mineral content (TLBMC) in control and propranolol-treated patients. Data are expressed as the odds ratios. *Significant difference at P< 0.05.

FIGURE 3

Effect of propranolol on body composition. (a) Percent change in central mass, (b) percent change in truncal fat, and (c) percent change in peripheral lean mass. In a-c, data are expressed as percent change from patient baseline and are shown as the Loess-smoothed trend with shading indicating SEM. (d, e) Comparison of the likelihood of losing ≥5% of (d) total bone mineral content/total body mass (TBMC/TBM) and (e) total lumbar bone mineral content (TLBMC) in control and propranolol-treated patients. Data are expressed as the odds ratios. *Significant difference at P< 0.05.

FIGURE 3

Effect of propranolol on body composition. (a) Percent change in central mass, (b) percent change in truncal fat, and (c) percent change in peripheral lean mass. In a-c, data are expressed as percent change from patient baseline and are shown as the Loess-smoothed trend with shading indicating SEM. (d, e) Comparison of the likelihood of losing ≥5% of (d) total bone mineral content/total body mass (TBMC/TBM) and (e) total lumbar bone mineral content (TLBMC) in control and propranolol-treated patients. Data are expressed as the odds ratios. *Significant difference at P< 0.05.

FIGURE 3

Effect of propranolol on body composition. (a) Percent change in central mass, (b) percent change in truncal fat, and (c) percent change in peripheral lean mass. In a-c, data are expressed as percent change from patient baseline and are shown as the Loess-smoothed trend with shading indicating SEM. (d, e) Comparison of the likelihood of losing ≥5% of (d) total bone mineral content/total body mass (TBMC/TBM) and (e) total lumbar bone mineral content (TLBMC) in control and propranolol-treated patients. Data are expressed as the odds ratios. *Significant difference at P< 0.05.

FIGURE 3

Effect of propranolol on body composition. (a) Percent change in central mass, (b) percent change in truncal fat, and (c) percent change in peripheral lean mass. In a-c, data are expressed as percent change from patient baseline and are shown as the Loess-smoothed trend with shading indicating SEM. (d, e) Comparison of the likelihood of losing ≥5% of (d) total bone mineral content/total body mass (TBMC/TBM) and (e) total lumbar bone mineral content (TLBMC) in control and propranolol-treated patients. Data are expressed as the odds ratios. *Significant difference at P< 0.05.